The overall objective is to gain insight and improve understanding of the antigenic structure of globular proteins. Globular proteins are a major class of natural antigens about which little chemical information is available. The structure of determinant groups in terms of specific numbers and kinds of participating amino acid residue side chains is generally unknown. In this laboratory a long term project has been initiated with the ultimate aim of providing this information. To this end proteins whose structure is completely known such as hemoglobin and cytochrome c have been used as model systems. The work achieved thus far indicates that these proteins are appropriate antigens for the intended purpose. By a study of cross reactions in cytochrome c and one amino acid mutants in human hemoglobin it has been possible to develop a tentative picture of the number and location of antigenic determinant groups in these particular antigens. These immunological studies have been supported and amplified by physicochemical measurements. This proposal deals with several approaches designed to penetrate further into the chemical nature of antigenic determinants of proteins and also to enhance our understanding of the structure of their corresponding antibodies. Enhanced knowledge of antigenic structure would provide useful information regarding the chemical requirements required for antigenic specificity in general and in particular might lead to the appropriate studies leading to our understanding of antigenic structure in such areas as transplantation immunology and vaccine development. Thus the study of globular protein antigens of known structure offers great promise for contributing to the understanding of fundamental problems in immunochemistry and immunobiology.